Alpha-1-antitrypsin is the major proteinase inhibitor in human sera. The most common form of this glycoprotein (i.e., the homozygote MM phenotype), as well as the homozygote ZZ phenotype which is associated with chronic obstructive lung disease, have been purified using classical chromatographic procedures. Each purified phenotypic protein exhibits a characteristic pattern of protein bonds on discontinuous acid starch gel electrophoresis. The major bands will be separated by isoelectric focusing. Variant peptides derived from the purified proteins after enzymic digestion will be compared after peptide mapping or column chromatography procedures by peptide sequencing. Carbohydrate containing peptides will be isolated by specific absorption on insolubilized Concanavalin A in combination with more conventional procedures (high voltage electrophoresis, ion-exchange chromatography). In addition, the secondary and tertiary structure of the native proteins and/or their complexes with enzymes will be probed by spectral, immunological, hydrodynamic, and chemical approaches. These studies are designed to establish the conformational and structural differences between proteins of the same phenotype as well as differences arising from genetic factors (i.e., between phenotypes). In addition, they are aimed at a further appreciation of the mechanism of inhibitory activity for alpha-1-antitrypsin.